Effect of amorphous phase separation and crystallization on the in vitro and in vivo performance of an amorphous solid dispersion.

In this study, the performance of phase separated and crystallized amorphous solid dispersions (ASDs) was evaluated by non-sink in vitro dissolution testing in fasted-state simulated intestinal fluid (FaSSIF) and in vivo in rats. The amorphous phase-separated or crystallized ASDs were prepared by mixing an ASD of the model drug celecoxib (CCX) in polyvinylpyrrolidone (PVP) with pure amorphous or micronized crystalline CCX at 20, 40, 60 or 100% of the total drug load (25:75 w/w CCX:PVP), respectively. As expected, crystallization of CCX in the ASDs generally had a negative influence on both the area under the curve of the dissolution curve (in vitro AUC) and the plasma concentration-time profile (in vivo AUC) in rats compared to the pure ASD. However, the difference between the in vivo AUC of the pure ASD and the 20% and 40% crystallized ASDs was not statistically significant, which could indicate that a low fraction of crystallization of a drug in an ASD may only have limited impact on in vivo performance and hence bioavailability. In comparison, amorphous phase separation of CCX in the ASDs did not negatively influence the in vitro AUC and in vivo AUC to the same degree as crystallization and the dissolution profiles of all the amorphous phase-separated ASDs were similar to that of the pure ASD. In fact, even though a slight decrease of in vivo AUC with increasing fraction of amorphous phase separation was observed, the 20% and 40% amorphous phase-separated ASDs were bioequivalent with the pure ASD.

The diagnosis of giardiasis.

Giardiasis is the most prevalent intestinal parasitic disease in the United States. Most cases can be diagnosed by a single stool examination. However, in periodic cyst excretors, cysts may not be detected unless repeated stool examinations are performed. In clinically highly suspected cases, duodenal fluid should be studies after three negative stool examinations. Scanning electron microscopy is probably superior to light microscopy in screening duodenal fluid if the parasite is scanty or degenerated. A small intestinal biopsy is a last resort for the diagnosis; a mucosal impression smear should be routinely performed on such specimens. The latter is the most sensitive and reliable technique in making the diagnosis.

Diagnosis of Strongyloides and hookworm infections: comparison of faecal and duodenal fluid microscopy.

Faecal microscopical diagnosis of Strongyloides and hookworm infections is insensitive. We have therefore compared duodenal fluid and faecal microscopy for detection of these parasites in a group of 292 patients being investigated for gastrointestinal symptoms who were examined by both techniques. Thirty-three of these patients (8%) were infected with Strongyloides stercoralis and 88 (30%) had hookworm infections. Microscopical examination of up to 3 faecal specimens detected only 33% and 65% of patients with Strongyloides and hookworm infections, respectively. Microscopical examination of a single specimen of duodenal fluid was more sensitive for detection of strongyloidiasis, identifying 76% of patients; the parasite was found exclusively in duodenal fluid (and not in faeces) in 67% of patients. For hookworm, the diagnostic sensitivity was similar with both techniques but duodenal fluid microscopy detected some patients (35%) who had not been identified by faecal microscopy. This study confirms previous work indicating the insensitivity of faecal microscopy in these infections and emphasizes the need to consider routine examination of duodenal fluid to exclude chronic strongyloidiasis. This may have particular relevance for south-east Asian war veterans and immunocompromised patients.

Detection of Giardia intestinalis in duodenal aspirate and in the stool.

Compared was the detection of Giardia intestinalis in duodenal contents and in the stool. During endoscopic examination duodenal contents were recovered by means of a tube attached to the mucosa and by aspiration from the region of pars verticalis. In 102 persons, duodenal and stool examinations revealed four and five cases of Giardia infection, respectively. The results showed that both diagnostic methods are equivalent and demonstrated that parasitologic examinations of patients suffering from dyspeptic disorders are very useful.

Giardiasis. Taming this pervasive parasitic infection.

Parasitic infection due to Giardia lamblia can produce severe, disabling gastrointestinal symptoms. Outbreaks have been linked to contaminated municipal water supplies and situations involving person-to-person contact. Immunocompromised patients are especially at risk. Because microscopic examination of stool detects the parasite in only about half of infected patients, use of enzyme-linked immunosorbent assay to detect Giardia-specific antigen is becoming increasingly popular. In most patients, therapy with quinacrine (Atabrine) hydrochloride, metronidazole (Flagyl, Protostat), or a combination of the two is effective.

Giardia lamblia in patients undergoing upper G.I. endoscopy.

To determine the frequency of giardiasis in patients undergoing upper G.I. endoscopy for dyspepsia and other upper G.I. disorders, duodenal aspirates were collected in 200 patients and simultaneous duodenal biopsies in 163 patients. Nine percent aspirates and 1.8% duodenal biopsies showed Giardia lamblia trophozoites. Giardia as a cause of dyspepsia should be considered in patients with negative endoscopy and in those who remain symptomatic inspite of adequate treatment for known upper G.I. disorders.

[Strongyloidosis. Part VIII. Parasitological diagnosis]. / Wegorczyca (strongyloidosis). Czesc VIII. Diagnostyka parazytologiczna.

The effectiveness and safety of the methods of detecting Strongyloides stercoralis, by passing larvae from the faeces to water, in duodenal fluid (duodenal intubation, Enterotest), in sputum and other body fluids, have been estimated. The author recommend Baermann technique for detecting S. stercoralis in individual examinations and Dancescu technique in mass field examinations. The detection of S. stercoralis larvae by the two methods ought to be checked by Fülleborn agar Petri dish technique in order to identify parasite to the species level.

[Giardiasis]. / Giardiasis.

Giardia Lamblia is considered as the most important cause of parasitic diarrhoea in children and adults. The epidemiology of the infection is determined by environmental and regional factors. The sensitivity of man for this infection depends on factors related to man himself and his environment. Structural changes of the gut such as cellular infiltration and villous atrophy, and functional derangements like malabsorption can explain part of the symptoms. The application of different procedures for the parasitological diagnosis with a variable degree of sensitivity is the cause of difference in recorded prevalence data. This infectious disease can be treated with a number of drugs; single dose treatment is to be preferred especially in childhood. Results of treatment i.a. with a single dose ornidazole are reported.

Intestinal mucus protects Giardia lamblia from killing by human milk.

We have previously shown that nonimmune human milk kills Giardia lamblia trophozoites in vitro. Killing requires a bile salt and the activity of the milk bile salt-stimulated lipase. We now show that human small-intestinal mucus protects trophozoites from killing by milk. Parasite survival increased with mucus concentration, but protection was overcome during longer incubation times or with greater milk concentrations. Trophozoites preincubated with mucus and then washed were not protected. Protective activity was associated with non-mucin CsCl density gradient fractions. Moreover, it was heat-stable, non-dialyzable, and non-lipid. Whereas whole mucus inhibited milk lipolytic activity, protective mucus fractions did not inhibit the enzyme. Furthermore, mucus partially protected G. lamblia trophozoites against the toxicity of oleic acid, a fatty acid which is released from milk triglycerides by lipase. These studies show that mucus protects G. lamblia both by inhibiting lipase activity and by decreasing the toxicity of products of lipolysis. The ability of mucus to protect G. lamblia from toxic lipolytic products may help to promote intestinal colonization by this parasite.

Migrational responses of Hymenolepis diminuta to surgical alteration of gastro-intestinal secretions.

The effects of the direction of gut flow, of injections of glucose and saline into different regions of the small intestine and of surgical re-routing or ligature of gastric, biliary and pancreatic secretions into the small intestine have been correlated with changes in the migratory response of the rat tapeworm Hymenolepis diminuta. Reversing the normal anterior to distal flow of luminal contents in the small intestine did not affect worm migration following feeding. Injections of a glucose-saline solution into the duodenum did not initiate a migratory response; similar injections into the mid- and posterior regions of the small intestine resulted in migrational responses similar to those following intragastric glucose feeding. Re-routing gastric secretions to the distal duodenum inhibited anterior migration of the worms beyond the new point of entry of gastric juices. Results following re-routing and ligation of the biliary and pancreatic secretions suggest that there is a potent cue to anteriad migration in the pancreatic secretions. Biliary secretions also appear to contain an additional migratory cue to worm migration. In order of importance the factors stimulating/inhibiting worm migration are pancreatic greater than gastric greater than biliary greater than glucose. The results support the hypothesis that the factors affecting worm distribution in the small intestine are interactive and synergistic, involve other luminal factors, such as 5-hydroxytryptamine and the physico-chemical gradients, and are of a regional nature such that the migratory response of a particular worm is directly related to its position in the small intestine when the cues to relocation are received.

Human giardiasis: correlation of specific secretory IgA levels in duodenal fluid to the severity of disease and infestation by Giardia lamblia.

Giardia lamblia specific secretory immunoglobulin A (sIgA) levels in the duodenal fluid of adult giardiasis cases are reported for the first time. The sIgA levels in the study group were found to be significantly higher (p less than 0.01) than in the 20 age- and sex-matched controls comprising cases classified as non-ulcerative dyspepsia who did nor reveal any G. lamblia in their stools and the duodenal fluid. An inverse relationship between the clinical severity of giardiasis and the level of sIgA in the duodenal fluid was noted. Cases with a higher trophozoite load in duodenal aspirate tended to be associated with envanescent G. lamblia-specific antibodies.